Leptospirosis is a worldwide zoonotic disease caused by gram-negative spirochetes belonging to the genus Leptospira. Leptospirosis is prevalent in humans, horses, cattle and wild animals. The disease occurs widely in developing countries, such as Brazil and India, and is re-emerging in developed countries. Although the incidence of leptospirosis in humans in the United States is relatively low, disease incidence in domestic animals has increased in recent years.
Manifestations and routes of Leptospira infection vary depending on the host. Humans, who contract leptospirosis either directly or indirectly through contact with infected animals or a contaminated environment, often develop kidney and liver failure (Schubert, G. E. et al., Munch Med Wochenschr, 113:80-86 (1971); Bain, B. J. et al., Arch. Intern. Med., 131:740-745 (1973); Garcia, M. et al., Med. Clin. (Barc), 73:362-366 (1979); San Segundo, D., Med. Clin. (Barc), 78:28-31 (1982); Winearls, C. G. et al., Q J Med., 53:487-495 (1984); Menzies, D. G. et al., Scott Med. J., 34:410 (1989); Divers, T. J. et al., J. Am. Vet. Med. Assoc., 201:1391-1392 (1992); Petros, S. et al., Scand. J. Infect. Dis., 32:104-105 (2000); Kager, P. A. et al., Ned Tijdschr Geneeskd, 145:184-186 (2001)). Leptospira infection in humans can range in severity from an inapparent infection to death from renal or hepatic failure (Feigin, R. D. and D. C. Anderson, CRC Crit. Rev. Clin. Lab. Sci., 5:413-467 (1975)). In addition to hepatic and renal failure, uveitis is sometimes a sequela to Leptospira infection (Rathinam, S. R. et al., Am. J. Ophthalmol., 124:71-79 (1997)).
In animals such as horses, cattle, dogs and swine, infection causes abortion, still birth, renal failure, and uveitis (Akkermans, J. P., Bull. Off. Int. Epizoot., 66:849-866 (1966); Ellis, W. A. et al., Vet. Rec., 99:458-459 (1976); Ryan, T. J. et al., NZ Vet. J., 25:352 (1977); Ellis, W. A. et al., Vet. Rec., 103:237-239 (1978); Andreani, E. et al., Br. Vet. J., 139:165-170 (1983); Ellis, W. A. et al., Vet. Rec., 112:291-293 (1983); Elder, J. K. et al., Aust. Vet. J., 62:258-262 (1985); Ellis, W. A. et al., Vet. Rec., 118:294-295 (1986); Rocha, T., Vet. Rec., 126:602 (1990); Bolin, C. A. et al., J. Vet. Diagn. Invest., 3:152-154 (1991); Donahue, J. M. et al., J. Vet. Diagn. Invest., 3:148-151 (1991); Christianson, W. T., Vet. Clin. North Am. Food Anim. Pract., 8:623-639 (1992); Donahue, J. M. et al., J. Vet. Diagn. Invest., 4:279-284 (1992); Bernard, W. V. et al., J. Am. Vet. Med. Assoc., 202:1285-1286 (1993); Broll, S. et al., Zentralbl Veterinarmed [B], 40:641-653 (1993); Donahue, J. M. et al., J. Vet. Diagn. Invest., 7:87-91 (1995); Donahue, J. M. and Williams, N. M., Vet. Clin. North Am. Equine Pract., 16:443-456 (2000)) and can result in multi-organ failure. In horses, the most common manifestations of infection are abortion and uveitis (Poonacha, K. B. et al., Vet. Pathol., 30:362-369 (1993)). The association of leptospires with equine recurrent uveitis (ERU) (Halliwell, R. E. et al., Curr. Eye Res., 4:1033-1040 (1985)) has been well documented and the organism has been detected in ocular fluids by culture and PCR (Roberts, S. J., J. Amer. Vet. Med. Assoc., 175:803-808 (1958)). In addition, Parma et al. demonstrated reactivity of several bands in extracts of equine cornea and lens with anti-leptospiral sera by western blotting (Parma, A. E. et al., Vet. Immunol. Immunopathol., 14:181-185 (1987); Parma, A. E. et al., Vet. Immunol. Immunopathol., 10:215-224 (1985)). Although there is a strong association between leptospiral infection and uveitis, the immunopathogenesis of Leptospira-associated uveitis remains obscure.
Currently available leptospiral vaccines have low efficacy, are serovar specific and generally produce only short-term immunity in domestic livestock. In fact, these vaccines do not provide cross protection against the 250 known serovars of pathogenic Leptospira. Efforts to identify immunogenic components of value in vaccines have resulted in characterization of 31, 32, 36 and 41 kDa outer membrane proteins (Haake, D. A. et al., J. Bacteriol., 175:4225-4234 (1993); Haake, D. A. et al., Infect. Immun., 68:2276-2285 (2000); Haake, D. A. et al., Infect. Immun., 66:1579-1587 (1998); Haake, D. A. et al., Infect. Immun., 67:6572-6582 (1999); Shang, E. S. et al., Infect. Immun., 65:3174-3181 (1995); Shang, E. S. et al., Infect. Immun., 64:2322-2330 (1996)). Two of these proteins (31 and 41 kDa) function synergistically in immunoprotection of hamsters suggesting that an effective protein based vaccine would contain several components (Haake, D. A. et al., Infect. Immun., 68:2276-2285 (2000)). The search for protective immunogens is complicated by the possibility that important components may be produced only during infection. Supporting this possibility are recent studies that indicate that some immunogenic proteins of L. interrogans serovar pomona are upregulated at 37° C. (Nally, J. E. et al., Infect. Immun., 69:400-404 (2001)).
Thus, there is an ongoing need for novel immunogenic proteins of Leptospira to aid in the development of effective vaccines and antibodies, as well as improved diagnostic methods and kits.